Possible Metastatic Stage-Dependent ILC2 Activation Induces Differential Functions of MDSCs through IL-13/IL-13Rα1 Signaling during the Progression of Breast Cancer Lung Metastasis

Breast cancer is the most common cancer in women worldwide, and lung metastasis is one of the most frequent distant metastases. When breast cancer metastasizes to the lung, group 2 innate lymphoid cells (ILC2s) are thought to promote tumor growth via the activation of myeloid-derived suppressor cells (MDSCs), which are known to negatively regulate anticancer immune responses. However, it remains to be elucidated exactly how this ILC2–MDSC interaction is involved in tumor growth during metastases formation. Using a 4T1/LM4 breast cancer mouse model, we found that ILC2s were activated in both the micro- and macrometastatic regions, suggesting sustained activation throughout the metastatic cascades via IL-33/ST2 signaling. Consistent with IL-13 secretion from activated ILC2s, the frequencies of polymorphonuclear (PMN)- and monocytic (M)-MDSCs were also significantly elevated during the progression from micro- to macrometastatic cancer. However, the effects of ILC2-induced MDSC functionality on the microenvironment differed in a metastatic-stage-specific manner. Our findings indicate that ILC2s may induce the immunosuppressive functions of MDSCs during the later stages of metastasis. Concomitantly, ILC2 may instigate extracellular matrix remodeling by PMN-MDSC activation during the early stages of metastasis. These metastatic-stage-specific changes may contribute to metastatic tumor growth in the microenvironment of breast cancer lung metastasis

Prenatal features of congenital peribronchial myofibroblastic tumor

Here, we report a case of a congenital peribronchial myofibroblastic tumor (CPMT). A 34-year-old primigravida was referred to our hospital at 31 gestation weeks because of suspected congenital pulmonary airway malformation (CPAM). Fetal ultrasonography showed a mass measuring 4.6 × 4.0 × 3.9 cm with mixed high and low echogenicity in the left lung, which was associated with microvascular blood flow in the tumor. Fetal magnetic resonance imaging (MRI) revealed a low-intensity left lobe lung lesion on a T2-weighted image. These findings suggested that the mass was a CPAM with atypical hypointense findings on MRI T2-weighted images or a rare primary pulmonary tumor, such as a CPMT. Unfortunately, the fetus died in utero at 34 gestation weeks due to cardiovascular failure, which could have resulted from direct encasement of the great vessels or cardiac compression due to rapid tumor growth. The autopsy findings confirmed the diagnosis of CPMT. Primary pulmonary tumors, such as CPMT, are extremely rare lung diseases that develop in utero. These tumors often rapidly grow during pregnancy, resulting in intrauterine fetal death. However, if the patient survives surgical mass resection, the prognosis is good. Given the adverse outcomes observed in our case, careful fetal monitoring is required in case of suspected CPMT during the third trimester of pregnancy. Moreover, in case the well-being of the fetus cannot be assured, immediate delivery should be considered, even in the preterm period, followed by surgery